PXD041837 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Involvement of extracellular vesicles in the progression, diagnosis, treatment, and prevention of whole-body ionizing radiation-induced immune dysfunction. |
Description | Acute radiation syndrome (ARS) is a severe condition that develops after exposure to high doses of ionizing radiation that features immune suppression and organ failure. Currently, there are no diagnostics to identify the occurrence or severity of radiation exposure. There are also no current treatments or preventative strategies to mitigate ARS. Extracellular vesicles (EVs) are mediators of intercellular communication that contribute to immune dysfunction across diseases. We investigated if EV cargo would be able to identify whole body irradiation (WBIR) exposure and if EVs promote ARS immune dysfunction. We hypothesized that beneficial EVs derived from mesenchymal stem cells (MSC-EVs) would blunt ARS immune dysfunction and might serve as prophylactic radioprotectants. Mice received WBIR (2 or 9 Gy) with assessment of EVs at 3 and 7 days after exposure. LC-MS/MS proteomic analysis of WBIR-EVs found dose-related changes as well as candidate proteins that were increased with both doses and timepoints (34 total) such as Thromboxane-A Synthase and lymphocyte cytosolic protein 2. Suprabasin and Sarcalumenin were increased only after 9 Gy suggesting these proteins may indicate high dose/lethal exposure. Analysis of EV miRNAs identified miR-376 and miR-136, which were increased up to 200- and 60-fold respectively by both levels of WBIR and select miRNAs such as miR-1839 and miR-664 that were increased only with 9 Gy. WBIR-EVs (9 Gy) were biologically active and blunted immune responses to LPS in RAW264.7 macrophages, inhibiting canonical signaling pathways associated with wound healing and phagosome formation. Accordingly, WBIR-EVs also blunted RAW macrophage phagocytosis. When given 3 days after exposure, MSC-EVs slightly modified immune gene expression changes in the spleens of mice in response to WBIR and a combined radiation plus burn injury exposure (RCI). MSC-EVs normalized the expression of certain key immune genes such as NFκBia and Cxcr4 (WBIR), Map4k1, Ccr9 and Cxcl12 (RCI) lowered plasma TNFα cytokine levels after RCI, though most gene changes were not influenced. When given prophylactically (24 and 3 hours before exposure), MSC-EVs prolonged survival to the 9 Gy lethal exposure. Thus, EVs are important participants in ARS. EV cargo might be used to diagnose WBIR exposure, and MSC-EVs might serve as radioprotectants to blunt the impact of toxic radiation exposure. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:51:36.105.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Angie Mordant |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-04-26 15:52:55 | ID requested | |
1 | 2023-06-30 12:26:40 | announced | |
⏵ 2 | 2024-10-22 05:51:36 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: acute radiation syndrome, mesenchymal stem cells, extracellular vesicles,Proteome, ionizing radiation, LC/MS-MS, immune dysfunction |
Contact List
Robert Maile |
contact affiliation | Surgery, University of Florida |
contact email | robert.maile@surgery.ufl.edu |
lab head | |
Angie Mordant |
contact affiliation | UNC Proteomics Core, Department of Pharmacology, University of North Carolina at Chapel Hill |
contact email | angie_mordant@med.unc.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041837
- Label: PRIDE project
- Name: Involvement of extracellular vesicles in the progression, diagnosis, treatment, and prevention of whole-body ionizing radiation-induced immune dysfunction.